Several processes have been used to produce 3-trifluoromethylacetophenone in the past; however, in all cases the yields have been low (70% or less), the volume efficiency of the processes have been low, and in some cases the product quality has been poor.
Examples include, U.S. Pat. No. 4,207,266, which teaches the reaction of 3-trifluoromethylbenzoyl chloride with the ethoxymagnesium derivative of diethyl malonate to form 3-trifluoromethylbenzoylmalonate. 3-Trifluoromethylbenzoylmalonate is then treated with aqueous acid to produce 3-trifluoromethylacetophenone in 60-70% yield.
Another example is set forth in CA 43:3361e-f, which discloses the addition of methyl Grignard reagent to 3-trifluoromethylphenyl cyanide, followed by acidification with aqueous acetic acid to form 3-trifluoromethylacetophenone in both poor quality and low yield.
A third example is described in Research Disclosure (1997), 402 (Oct) P706 (No. 40221), (CA 127:294925h). This reference teaches the multi-step reaction of 3-trifluoromethylaniline sequentially with a) aqueous sulfuric acid, b) aqueous sodium nitrite, c) aqueous acetaldoxime, d) cuprous sulfate and sodium bicarbonate and e) hydrochloric acid to form 3-trifluoromethylacetophenone in 70% yield. However, the overall volume efficiency of this process scheme is very low.
A fourth reference, Research Disclosure (1996), 386, 348 (CA 125:114257), teaches the reaction of 3-trifluoromethylbromobenzene with magnesium to produce the corresponding Grignard reagent followed by reaction with acetic anhydride and finally with aqueous acetic acid to form 3-trifluoromethylacetophenone. The yield of product from this reaction is about 60%; however, this Grignard reaction is known to be unstable and can decompose explosively. In addition, the reaction with acetic anhydride has to be run very cold, at about 0.degree. C., thus making this route not commercially appealing.
In summary, all of the prior art processes for producing 3-trifluoromethylacetophenone have significant drawbacks. Accordingly, it would represent a notable advance in the state of the art if a simple and efficient process to provide 3-trifluoromethylacetophenone in high yield and high purity starting with readily commercially available reagents were provided.